PB2219: POLYPHARMACY AND DRUG-TO-DRUG INTERACTIONS MAY HAVE A NEGATIVE EFFECT ON SURVIVAL IN PATIENTS WITH CHRONIC MYELOPROLIFERATIVE NEOPLASMS
Authors: Ivan Krecak, Ljerka Pivac, Eva Cubric, Marko Lucijanic, Marko Skelin
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Polypharmacy, potentially inappropriate medications (PIM), and drug-to-drug interactions (DDI) are frequent among elderly persons and are associated with adverse clinical outcomes. Chronic myeloproliferative neoplasm (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are hematopoietic stem cell disorders typically diagnosed in the elderly and carry a high cardiovascular (CV) risk. Aims: To investigate frequencies of polypharmacy, PIM, and DDI among MPN patients and their effect on overall survival (OS). Methods: This was a study conducted at General Hospital of Sibenik-Knin County, Croatia. Patients with MPNs whose disease diagnosis was reassessed according to 2016 WHO criteria were retrospectively included in the period between 1996 and 2022. Clinical and laboratory data was recorded through medical chart review. CV risk factors considered were arterial hypertension, active smoking, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Chronic heart failure (CHF) was defined as EF<50% or the need for diuretic use. Polypharmacy was defined as simultaneous use of ≥5 medications. PIM were defined according to EU(7)-PIM list; these medications are defined as those which should be avoided in the elderly due to high-risk of adverse events and/or insufficient evidence of their benefit and when there are equally or more effective but lower risk alternatives available. DDI were defined using the Lexicomp Drug Interaction Analysis. This study focused solely on C (monitor therapy), D (modify regimen) and X interactions (avoid combination). Categorical variables were compared with the chi-square test. Survival analyses were performed with Kaplan-Meier and the Cox-regression analysis. Results: A total of 124 MPN patients (ET=63, PV=44, MF=9, MPN-u=8) were included; median age was 70 years (range 21-92) and 76 (61.3%) were females. Polypharmacy, PIMs (calculated for persons >60 years of age, n=101), and DDIs were recorded in 76 (61.3%), 46 (45.5%) and 77 (62.1%) of patients, respectively. The median number of prescribed medications, PIMs, C, and D was 5 (range 0-16), 0 (range 0-4), 3 (range 1-20), and 1 (range 1-4), respectively. No X interactions were found. Polypharmacy and DDI were associated with the presence of older age, constitutional symptoms, osteoarthritis/osteoporosis, oral anticoagulants, arterial hypertension, hyperlipidemia, and CHF, whereas the use of PIM correlated with older age, peptic ulcer disease, osteoarthritis/osteoporosis, and psychiatric disorders (p<0.050 for all analyses). Considering the small number of MF and MPN-u patients included, during survival analyses we focused solely on ET and PV patients (n=108) whose OS (p=0.398) did not differ. Univariately, polypharmacy (HR 2.30, p=0.002) and DDI (HR 2.00, p=0.035) had a negative effect on OS, as shown in Figure 1. In the multivariate analyses adjusted for sex, disease phenotype, baseline leukocytosis, and cytoreductive treatment, independent predictors of an inferior OS were high-risk disease (<0.050), CV risk factors (p<0.050), polypharmacy (HR 5.22, p=0.022) and DDI (HR 4.88, p=0.027). Summary/Conclusion: Polypharmacy, PIM and DDI are very frequent among MPN patients and are mostly associated with MPN-related symptoms, osteoarthritis/osteoporosis, oral anticoagulants, and different CV disorders. More importantly, polypharmacy and DDI were shown to be independent predictors of inferior OS in ET and PV. Therefore, clinicians caring for MPNs should stay vigilant and tactful in managing disease-related symptoms and to periodically reassess medications used to treat patients’ other clinical conditions in order to avoid medication overuse and potentially inadvertent DDI.Keywords: Survival, Myeloid malignancies, Myeloproliferative disorder, Therapy